Asymmetric Sensitivity of Hepatic Venous Pressure Gradient to Portal and Sinusoidal Resistance: An In Vitro Experimental Study

Hepatic venous pressure gradient (HVPG) is the clinical gold standard for assessing portal hypertension, but its dependence on different vascular resistance sources remains unclear. This study evaluated the respective effects of sinusoidal resistance (SR) and portal venous resistance (PVR) on HVPG using an in vitro hemodynamic platform. A mock circulatory loop with dual hepatic blood supply was constructed and calibrated to near-physiological conditions. SR and PVR were independently adjusted to reproduce different portal hypertension states, and HVPG was measured by balloon wedging. A perturbation index (PI) was introduced to quantify the systemic effect of wedging, and Sobol global sensitivity analysis was used to compare resistance contributions. HVPG increased markedly with SR, ranging from 3.69 to 12.25 mmHg, but showed only limited changes with PVR, ranging from 1.03 to 6.56 mmHg. Sobol analysis confirmed the dominant contribution of SR over PVR (S1: 0.856 vs. 0.034). Balloon wedging also induced measurable systemic perturbations, particularly under high-resistance conditions. Overall, HVPG is highly sensitive to SR but relatively insensitive to PVR, indicating a systematic underestimation risk in presinusoidal portal hypertension. Moreover, the hemodynamic perturbation induced by balloon wedging should not be neglected in severe portal hypertension, suggesting that this effect should be incorporated into virtual HVPG models to improve their predictive accuracy.